Basal cell carcinoma (BCC) is the most common human cancer, primarily seen in Caucasians. The cumulative amount of ultra-violet light (UVL) exposure and the type of skin play a major role in the development of BCC. It has been demonstrated that the development of BCC is an ongoing process and that the occurrence of new lesions is influenced by the number of previous BCC, thus allowing projection of the incidence of new BCC in patients with skin cancers. Because of these characteristics BCC represents as an ideal model of human cancer for the study of cancer chemo-preventive agents. The objective of the proposed project is to determine the effect of oral administration of beta carotene alone or in combination with ascorbic acid and alpha-tocoperol in patients at high risks for multiple BCC. The proposed project is designed: 1) To study whether these agents alone or in combination may reduce the occurrence of new tumors; this will be done by randomizing patients with a past history of multiple BCC into three groups and treating them with beta carotene alone, beta-carotene plus ascorbic acid and alpha-tocopherol or placebo in a double blind fashion; 2) to determine the role immunologic and genetic factors in BCC. HLA typing and serial determinations of lymphocyte proliferative responses will be evaluated in each patient and analyzed in connection with the clinical findings; 3) to evaluate the possible influence of chemopreventive agents on host immunity by correlating the immunologic and clinical data accummulated during the course of therapy. The long term objective of the project is aimed at a better understanding of the influence of chemo-preventive agents on skin cancer, and the development of effective skin cancer chemo-prevention.